The need for understanding essential recognition events in chemistry and biology has directed considerable efforts toward the development of chemical probes. Fluorescent probes are attractive and versatile tools for both analytical sensing and optical imaging because of their high sensitivity, fast response time, and technical simplicity. However, the mechanisms that regulate the interaction between fluorescent probes and their targets are often poorly understood; hence, the ability to predict structural requirements and to design new probes using theoretical calculations is limited. Combinatorial approaches have recently boosted the generation and optimization of fluorescent probes, especially for complex scientific problems that remain indefinite at the molecular recognition level. The development of combinatorial strategies for derivatizing known fluorescent scaffolds with commercially available building blocks using conventional synthetic procedures would enable access to a broader scope of fluorescent probes.
The development of fluorescent and molecular imaging probes based on the BODIPY scaffold has been widely exploited due to its outstanding fluorescent properties (e.g. high photostability, extinction coefficients and quantum yields, tunable excitation and emission spectra) (1-7) and facile conversion into probes for Positron Emission Tomography (PET) imaging (8,9). Most methods to derivatize the 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY) scaffold involve solution-phase chemistry, which often requires tedious purification steps (10). Efforts to derivatize BODIPY on solid-phase have been hampered by its lability in both acidic and basic conditions (11).
There is a need to develop methods to rapidly achieve new compound libraries based on useful fluorescent scaffolds, such as the BODIPY-based scaffold. Moreover, within these libraries, there is a need to develop selective and specific probes for various analytes with critical biological functions.